D-allulose, also known by the name D-psicose or just allulose, is a rare keto-sugar epimer of D-fructose in the third carbon (C3), and naturally occurs in small quantity in fruits such as grapes and figs. It is low calorie sweetener produced enzymatically from D-fructose by enzymes D-ketose 3-epimerase (DKEase) family. D-allulose has a similar taste, texture and functionality as sweetener comparing to high calorie sweetener sugar table sucrose. D-allulose is poorly metabolized in the body with minimal impact on blood sugar levels making it a natural low-calorie sweetener. This property makes D-allulose an attractive sweetener for diabetes and for body weight management. Laboratory studies on D-allulose intake demonstrated its safety with no significant adverse effects. United States Food and Drug Administration (FDA) has granted D-allulose the status of Generally Recognized as Safe (GRAS). Plus, it is considered safe for human consumption by regulatory organizations in other countries except in European Union due to their request for further laboratory testing. Maximum acceptable daily intake of D-allulose is 0.9 grams per kilogram body weight. Excessive intake for more than the recommended daily intake could lead to some side effects such as gastrointestinal discomfort or laxative effects. In general, D-allulose is considered one of the preferred natural low calories sweeteners for those seeking an alternative to table sugar sucrose.
References
[1]
Bolger, A.M., Rastall, R.A., Oruna-Concha, M.J. and Rodriguez-Garcia, J. (2021) Effect of D-Allulose, in Comparison to Sucrose and D-Fructose, on the Physical Properties of Cupcakes. Lebensmittel-Wissenschaft & Technologie, 150, Article 111989. https://doi.org/10.1016/j.lwt.2021.111989
[2]
Hossain, A., Tsukamoto, I., Yamaguchi, F., Hirata, Y., Dong, Y., Kamitori, K., et al. (2014) Intestinal Absorption, Organ Distribution, and Urinary Excretion of the Rare Sugar D-Psicose. Drug Design, Development and Therapy, 2014, 1955-1964. https://doi.org/10.2147/dddt.s60247
[3]
Chung, M., Oh, D. and Lee, K.W. (2012) Hypoglycemic Health Benefits of D-Psicose. Journal of Agricultural and Food Chemistry, 60, 863-869. https://doi.org/10.1021/jf204050w
[4]
Kim, S., Kim, S.J., Kim, H. and Sung, M. (2017) D-Psicose, a Sugar Substitute, Suppresses Body Fat Deposition by Altering Networks of Inflammatory Response and Lipid Metabolism in C57BL/6J-ob/ob Mice. Journal of Functional Foods, 28, 265-274. https://doi.org/10.1016/j.jff.2016.11.029
[5]
Bilik, V. and Tihlarik, K. (1973) Reaction of Saccharides Catalyzed by Molybdate Ions. IX. Epimerization of Ketohexoses. Chemical Papers, 28, 106-109.
[6]
Doner, L.W. (1979) Isomerization of D-Fructose by Base: Liquid-Chromatographic Evaluation and the Isolation of D-Psicose. Carbohydrate Research, 70, 209-216. https://doi.org/10.1016/s0008-6215(00)87101-3
[7]
Kim, H., Hyun, E., Kim, Y., Lee, Y. and Oh, D. (2006) Characterization of an Agrobacterium Tumefaciens D-Psicose 3-Epimerase That Converts D-Fructose to D-Psicose. Applied and Environmental Microbiology, 72, 981-985. https://doi.org/10.1128/aem.72.2.981-985.2006
[8]
Itoh, H., Okaya, H., Khan, A.R., Tajima, S., Hayakawa, S. and Izumori, K. (1994) Purification and Characterization of D-Tagatose 3-Epimerase from Pseudomonas sp. ST-24. Bioscience, Biotechnology, and Biochemistry, 58, 2168-2171. https://doi.org/10.1271/bbb.58.2168
[9]
Mu, W., Chu, F. and Jiang, B. (2010) Characterization of a Novel D-Tagatose 3-Epimerase from Clostridium scindens ATCC 35704. Journal of Biotechnology, 150, 536-537. https://doi.org/10.1016/j.jbiotec.2010.09.878
[10]
Zhang, W., Zhang, T., Jiang, B. and Mu, W. (2015) Biochemical Characterization of a D-Psicose 3-Epimerase from Treponema Primitiazas-1 and Its Application on Enzymatic Production of D-Psicose. Journal of the Science of Food and Agriculture, 96, 49-56. https://doi.org/10.1002/jsfa.7187
[11]
Zhu, Z., Li, L., Zhang, W., Li, C., Mao, S., Lu, F., et al. (2021) Improving the Enzyme Property of D-Allulose 3-Epimerase from a Thermophilic Organism of Halanaerobium Congolense through Rational Design. Enzyme and Microbial Technology, 149, Article 109850. https://doi.org/10.1016/j.enzmictec.2021.109850
[12]
Zhu, Z., Li, C., Liu, X., Gao, D., Wang, X., Tanokura, M., et al. (2019) Biochemical Characterization and Biocatalytic Application of a Novel D-Tagatose 3-Epimerase from Sinorhizobium sp. RSC Advances, 9, 2919-2927. https://doi.org/10.1039/c8ra10029b
[13]
Chen, J., Ni, D., Xu, W., Zhang, W. and Mu, W. (2024) Recent Advances in Discovery, Protein Engineering, and Heterologous Production of Ketose 3-Epimerase for Rare Sugar Biosynthesis. Trends in Food Science & Technology, 149, Article 104552. https://doi.org/10.1016/j.tifs.2024.104552
[14]
Tan, J.H., Chen, A., Bi, J., Lim, Y.H., Wong, F.T. and Ow, D.S. (2023) The Engineering, Expression, and Immobilization of Epimerases for D-Allulose Production. International Journal of Molecular Sciences, 24, Article 12703. https://doi.org/10.3390/ijms241612703
[15]
Zhang, W., Jia, M., Yu, S., Zhang, T., Zhou, L., Jiang, B., et al. (2016) Improving the Thermostability and Catalytic Efficiency of the D-Psicose 3-Epimerase from Clostridium bolteae ATCC BAA-613 Using Site-Directed Mutagenesis. Journal of Agricultural and Food Chemistry, 64, 3386-3393. https://doi.org/10.1021/acs.jafc.6b01058
[16]
Patel, S.N., Kaushal, G. and Singh, S.P. (2021) D-Allulose 3-Epimerase of Bacillus Sp. Origin Manifests Profuse Heat-Stability and Noteworthy Potential of D-Fructose Epimerization. Microbial Cell Factories, 20, Article No. 60. https://doi.org/10.1186/s12934-021-01550-1
[17]
Yoshida, H., Yoshihara, A., Kato, S., Mochizuki, S., Akimitsu, K., Izumori, K., et al. (2021) Crystal Structure of a Novel Homodimeric l-Ribulose 3-Epimerase from Methylomonus sp. FEBS Open Bio, 11, 1621-1637. https://doi.org/10.1002/2211-5463.13159
[18]
Mu, W., Chu, F., Xing, Q., Yu, S., Zhou, L. and Jiang, B. (2011) Cloning, Expression, and Characterization of a D-Psicose 3-Epimerase from Clostridium cellulolyticum H10. Journal of Agricultural and Food Chemistry, 59, 7785-7792. https://doi.org/10.1021/jf201356q
[19]
Choi, J., Ju, Y., Yeom, S. and Oh, D. (2011) Improvement in the Thermostability of D-Psicose 3-Epimerase from Agrobacterium Tumefaciens by Random and Site-Directed Mutagenesis. Applied and Environmental Microbiology, 77, 7316-7320. https://doi.org/10.1128/aem.05566-11
[20]
Kim, N., Kim, H., Kang, D., Jeong, K., Lee, J., Kim, Y., et al. (2008) Conversion Shift of d-Fructose to d-Psicose for Enzyme-Catalyzed Epimerization by Addition of Borate. Applied and Environmental Microbiology, 74, 3008-3013. https://doi.org/10.1128/aem.00249-08
[21]
Van Duc Long, N., Le, T., Kim, J., Lee, J.W. and Koo, Y. (2009) Separation of D-Psicose and D-fructose Using Simulated Moving Bed Chromatography. Journal of Separation Science, 32, 1987-1995. https://doi.org/10.1002/jssc.200800753
[22]
Itoh, H., Sato, T. and Izumori, K. (1995) Preparation of D-Psicose from D-Fructose by Immobilized D-Tagatose 3-Epimerase. Journal of Fermentation and Bioengineering, 80, 101-103. https://doi.org/10.1016/0922-338x(95)98186-o
[23]
Wang, J., Sun, J., Qi, H., Wang, L., Wang, J. and Li, C. (2021) High Production of D-psicose from D-fructose by Immobilized Whole Recombinant Bacillus subtilis Cells Expressing D-Psicose 3-Epimerase from Agrobacterium tumefaciens. Biotechnology and Applied Biochemistry, 69, 364-375. https://doi.org/10.1002/bab.2115
[24]
Yang, J., Fan, D., Zhao, F., Lin, Y., Zheng, S. and Han, S. (2022) Characterization of D-Allulose-3-Epimerase from Ruminiclostridiumpapyrosolvens and Immobilization within Metal-Organic Frameworks. Frontiers in Bioengineering and Biotechnology, 10, Article 869536. https://doi.org/10.3389/fbioe.2022.869536
[25]
Bu, Y., Zhang, T., Jiang, B. and Chen, J. (2021) Improved Performance of D-Psicose 3-Epimerase by Immobilisation on Amino-Epoxide Support with Intense Multipoint Attachment. Foods, 10, Article 831. https://doi.org/10.3390/foods10040831
[26]
Wulansari, S., Heng, S., Ketbot, P., Baramee, S., Waeonukul, R., Pason, P., et al. (2023) A Novel D-Psicose 3-Epimerase from Halophilic, Anaerobic Iocasiafonsfrigidae and Its Application in Coconut Water. International Journal of Molecular Sciences, 24, Article 6394. https://doi.org/10.3390/ijms24076394
Eş, I., Vieira, J.D.G. and Amaral, A.C. (2015) Principles, Techniques, and Applications of Biocatalyst Immobilization for Industrial Application. Applied Microbiology and Biotechnology, 99, 2065-2082. https://doi.org/10.1007/s00253-015-6390-y
[29]
Singh, R., Tiwari, M., Singh, R. and Lee, J. (2013) From Protein Engineering to Immobilization: Promising Strategies for the Upgrade of Industrial Enzymes. International Journal of Molecular Sciences, 14, 1232-1277. https://doi.org/10.3390/ijms14011232
[30]
Wang, J., Sun, J., Qi, H., Wang, L., Wang, J. and Li, C. (2021) High Production of D-Psicose from D-Fructose by Immobilized Whole Recombinant Bacillus subtilis Cells Expressing d-Psicose 3-Epimerase from Agrobacterium tumefaciens. Biotechnology and Applied Biochemistry, 69, 364-375. https://doi.org/10.1002/bab.2115
[31]
Xia, Y., Cheng, Q., Mu, W., Hu, X., Sun, Z., Qiu, Y., et al. (2021) Research Advances of D-Allulose: An Overview of Physiological Functions, Enzymatic Biotransformation Technologies, and Production Processes. Foods, 10, Article 2186. https://doi.org/10.3390/foods10092186
[32]
Guo, Q., Liu, C., Zheng, L., Zheng, S., Zhang, Y., Zhao, S., et al. (2022) Metabolically Engineered Escherichia Coli for Conversion of D-Fructose to D-Allulose via Phosphorylation-Dephosphorylation. Frontiers in Bioengineering and Biotechnology, 10, Article 947469. https://doi.org/10.3389/fbioe.2022.947469
[33]
Kornberg, H.L. (2001) Routes for Fructose Utilization by Escherichia coli. Microbiology & Molecular Biotechnology, 3, 355-359.
[34]
Saier Jr., M.H. (2015) The Bacterial Phosphotransferase System: New Frontiers 50 Years after Its Discovery. Microbial Physiology, 25, 73-78. https://doi.org/10.1159/000381215
[35]
Guo, Q., Zheng, L., Luo, X., Gao, X., Liu, C., Deng, L., et al. (2021) Engineering Escherichia coli for D-Allulose Production from D-Fructose by Fermentation. Journal of Agricultural and Food Chemistry, 69, 13578-13585. https://doi.org/10.1021/acs.jafc.1c05200
[36]
Taylor, J.E., Palur, D.S.K., Zhang, A., Gonzales, J.N., Arredondo, A., Coulther, T.A., et al. (2023) Awakening the Natural Capability of Psicose Production in Escherichia coli. npj Science of Food, 7, Article No. 54. https://doi.org/10.1038/s41538-023-00231-0
[37]
Kornberg, H.L., Lambourne, L.T.M. and Sproul, A.A. (2000) Facilitated Diffusion of Fructose via the Phosphoenolpyruvate/glucose Phosphotransferase System of Escherichia coli. Proceedings of the National Academy of Sciences, 97, 1808-1812. https://doi.org/10.1073/pnas.97.4.1808
[38]
Chen, Z., Gao, X. and Li, Z. (2022) Recent Advances Regarding the Physiological Functions and Biosynthesis of D-Allulose. Frontiers in Microbiology, 13, Article 881037. https://doi.org/10.3389/fmicb.2022.881037
[39]
Wen, X., Ning, Y., Lin, H., Ren, Y., Li, C., Liu, Y., et al. (2022) D-Allulose (D-Psicose) Biotransformation from D-Glucose, Separation by Simulated Moving Bed Chromatography (SMBC) and Purification by Crystallization. Process Biochemistry, 119, 29-38. https://doi.org/10.1016/j.procbio.2022.05.013
[40]
Morita, T., El-Kazzaz, W., Tanaka, Y., Inada, T. and Aiba, H. (2003) Accumulation of Glucose 6-Phosphate or Fructose 6-Phosphate Is Responsible for Destabilization of Glucose Transporter mRNA Inescherichia coli. Journal of Biological Chemistry, 278, 15608-15614. https://doi.org/10.1074/jbc.m300177200
[41]
Guo, Y., Zhu, Z., Lv, J., Li, Y., Chen, J., Cheng, X., et al. (2023) Irreversible Biosynthesis of D-Allulose from D-Glucose in Escherichia coli through Fine-Tuning of Carbon Flux and Cofactor Regeneration Engineering. Journal of the Science of Food and Agriculture, 103, 5481-5489. https://doi.org/10.1002/jsfa.12623
[42]
Guo, Q., Zheng, L., Zheng, S., Zheng, H., Lin, X. and Fan, L. (2024) Enhanced Biosynthesis of D-Allulose from a D-Xylose-Methanol Mixture and Its Self-Inductive Detoxification by Using Antisense RNAs in Escherichia coli. Journal of Agricultural and Food Chemistry, 72, 14821-14829. https://doi.org/10.1021/acs.jafc.4c03219
[43]
Takeshita, K., Suga, A., Takada, G. and Izumori, K. (2000) Mass Production of D-Psicose from D-Fructose by a Continuous Bioreactor System Using Immobilized D-Tagatose 3-Epimerase. Journal of Bioscience and Bioengineering, 90, 453-455. https://doi.org/10.1016/s1389-1723(01)80018-9
[44]
Huang, Y., Li, L., Chi, Y., Sha, Y., Wang, R., Xu, Z., et al. (2020) Fusion and Secretory Expression of an Exo-Inulinase and a D-Allulose 3-Epimerase to Produce D-Allulose Syrup from Inulin. Journal of the Science of Food and Agriculture, 101, 693-702. https://doi.org/10.1002/jsfa.10682
[45]
Xin, D. and Ran, G. (2024) Strategy for Production of High-Purity Rare Sugar D-Allulose from Corn Stover. Journal of Cleaner Production, 439, Article 140717. https://doi.org/10.1016/j.jclepro.2024.140717
[46]
Zhang, J., Xu, C., Chen, X., Ruan, X., Zhang, Y., Xu, H., et al. (2020) Engineered Bacillus Subtilis Harbouring Gene of D-Tagatose 3-Epimerase for the Bioconversion of D-Fructose into D-Psicose through Fermentation. Enzyme and Microbial Technology, 136, Article 109531. https://doi.org/10.1016/j.enzmictec.2020.109531
[47]
Zhang, L., Jiang, B., Mu, W. and Zhang, T. (2009) Bioproduction of D-Psicose Using Permeabilized Cells of Newly Isolated Rhodobactersphaeroides SK011. Frontiers of Chemical Engineering in China, 3, 393-398. https://doi.org/10.1007/s11705-009-0252-z
[48]
Takeshita, K., Suga, A., Takada, G. and Izumori, K. (2000) Mass Production of D-Psicose from D-Fructose by a Continuous Bioreactor System Using Immobilized D-Tagatose 3-Epimerase. Journal of Bioscience and Bioengineering, 90, 453-455. https://doi.org/10.1263/jbb.90.453
[49]
Song, Y., Nguyen, Q.A., Wi, S.G., Yang, J. and Bae, H. (2017) Strategy for Dual Production of Bioethanol and D-Psicose as Value-Added Products from Cruciferous Vegetable Residue. Bioresource Technology, 223, 34-39. https://doi.org/10.1016/j.biortech.2016.10.021
[50]
Itoh, H., Okaya, H., Khan, A.R., Tajima, S., Hayakawa, S. and Izumori, K. (1994) Purification and Characterization of D-Tagatose 3-Epimerase from Pseudomonas sp. ST-24. Bioscience, Biotechnology, and Biochemistry, 58, 2168-2171. https://doi.org/10.1271/bbb.58.2168
[51]
Daniel, H., Hauner, H., Hornef, M. and Clavel, T. (2021) Allulose in Human Diet: The Knowns and the Unknowns. British Journal of Nutrition, 128, 172-178. https://doi.org/10.1017/s0007114521003172
[52]
Jürkenbeck, K., Haarhoff, T., Spiller, A. and Schulze, M. (2022) Does Allulose Appeal to Consumers? Results from a Discrete Choice Experiment in Germany. Nutrients, 14, Article 3350. https://doi.org/10.3390/nu14163350
[53]
Baek, S.H., Kwon, S.Y. Lee, H.G. and Baek, H.H. (2008) Maillard Browning Reaction of D-Psicose as Affected by Reaction Factors. Food Science and Biotechnology, 17, 1349-1351.
[54]
Özgür, M., Özgür, E.B. and Dinçoğlu, A.H. (2022) Prebiotic Effect of D-Allulose (D-Psicose): Traditional Review. TurkiyeKlinikleri Journal of Health Sciences, 7, 573-577. https://doi.org/10.5336/healthsci.2021-84078
[55]
Matsuo, T., Yokoyama, C., Yamada, T., Iida, T., Mochizuki, S., Yoshihara, A., et al. (2024) Anti-Obesity Effects of Dietary D-Allulose and Medium-Chain Triglycerides in High-Fat Diet-Fed Rats. Food and Nutrition Sciences, 15, 701-710. https://doi.org/10.4236/fns.2024.158045
[56]
Choi, M.N., Shin, K., Kim, D.W., Kim, B., Park, C., Yeom, S., et al. (2021) Production of D-Allose from D-Allulose Using Commercial Immobilized Glucose Isomerase. Frontiers in Bioengineering and Biotechnology, 9, Article 681253. https://doi.org/10.3389/fbioe.2021.681253
[57]
Wen, X., Lin, H., Ren, Y., Li, C., Zhang, C., Lin, J., et al. (2022) Allitol Bioproduction by Recombinant Escherichia Coli with NADH Regeneration System Co-Expressing Ribitol Dehydrogenase (RDH) and Formate Dehydrogenase (FDH) in Individual or in Fusion. Electronic Journal of Biotechnology, 55, 91-98. https://doi.org/10.1016/j.ejbt.2021.11.007
